COVID-19 lockdown and association with placental function – a quasi-experimental analysis

PREPARE Consortium

doi:10.1016/j.preghy.2026.101452

COVID-19 lockdown and association with placental function – a quasi-experimental analysis

PREPARE Consortium

Research output: Contribution to Journal › Article › Academic › peer-review

Abstract

Objective: To evaluate the effect of COVID-19 lockdown measures on the occurrence of hypertensive disorders of pregnancy and fetal growth restriction in a national pregnancy population.

Study design: This is a national registry-based quasi-experimental study, including singleton births ≥24 + 0 weeks from nulliparous women between 2016–2020. We evaluated the effect of gestational age upon entering the first nationwide lockdown period (March 9th–June 1st 2020) on outcome. This effect can be assumed to be unconfounded (a so-called quasi-experimental analysis), because this period was unexpected and implemented rapidly, minimizing anticipatory changes at population level.

Main outcome measures: Primary outcomes were hypertensive disorders of pregnancy (including pre-eclampsia) and small-for-gestational-age (birthweight <10th Hoftiezer percentile), as proxy for fetal growth restriction.

Results: The analysis included 262,102 pregnancies. Compared to previous years, entering the lockdown in the first trimester was associated with an absolute +0.4% risk of hypertensive disorders of pregnancy (95%CI: +0.0% – +0.8%), +0.2% risk of pre-eclampsia (95%CI: +0.0% – +0.4%), but −0.5% risk of small-for-gestational-age (95%CI: −1.2 – –0.3). There was less evidence that other evaluated periods and trimesters were associated with the outcome.

Conclusion: Being exposed to COVID 19 lockdown was associated with a slight increase in hypertensive disorders of pregnancy, including pre-eclampsia, but a counterintuitive trend towards lower risk for small-for-gestational-age. Because the effect was most clear in the first trimester, the nationwide lockdown therefore seems to have a complex effect on the in-utero environment through the placenta.

Original language	English
Article number	101452
Pages (from-to)	1-9
Number of pages	9
Journal	Pregnancy Hypertension
Volume	44
Early online date	11 Mar 2026
DOIs	https://doi.org/10.1016/j.preghy.2026.101452
Publication status	Published - Jun 2026

Bibliographical note

Publisher Copyright:
© 2026 The Author(s). Published by Elsevier B.V. on behalf of International Society for the Study of Hypertension in Pregnancy. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

Funding

This project was supported by ZonMW (Grant #05160482210001), Chiesi Pharmaceuticals, de Snoo-van ‘t Hoogerhuijs Foundation, and Strong Babies. The funders of the study were not involved in the study design, data collection, data analysis, interpretation, or the writing of the manuscript. The PREPARE consortium comprises of the following members:Elena Ambrosino – Institute for Public Health Genomics (IPHG), Department of Genetics and Cell Biology, Faculty of Health, Medicine & Life Sciences, Maastricht University, Maastricht, The Netherlands; Research School GROW for Oncology and Reproduction, Maastricht University, Maastricht, The Netherlands.Kim Vanden Auweele- HELLP stichting, the Netherlands.Jasper Been – Department of Obstetrics and Gynaecology, Division of Obstetrics and Fetal Medicine, Erasmus MC Sophia Children’s Hospital, University Medical Centre Rotterdam, Rotterdam, The Netherlands; Department of Neonatal and Paediatric Intensive Care, Division of Neonatology, Erasmus MC Sophia Children’s Hospital, University Medical Centre Rotterdam, Rotterdam, The Netherlands; Department of Public Health, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, The Netherlands.Roseriet Beijers – Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, the Netherlands; Behavioural Science Institute, Radboud University, Nijmegen, the Netherlands.Loes Bertens – Department of Obstetrics and Gynaecology, Erasmus University Medical Centre, the Netherlands.Kitty Bloemenkamp – Department of Obstetrics, Wilhelmina’s Children Hospital Birth Centre, Division Woman and Baby, University Medical Centre Utrecht, Utrecht, the Netherlands.Nienke Boderie – Department of Public Health, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands.Lex Burdorf – Department of Public Health, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands.Lizbeth Burgos Ochoa – Department of Methodology and Statistics, Tilburg University, Tilburg, the Netherlands; Department of Obstetrics and Gynaecology, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands.Ank de Jonge – Department of Midwifery Science, Amsterdam University Medical Centre, Amsterdam, the Netherlands; Midwifery Academy Amsterdam Groningen, InHolland, Amsterdam, the Netherlands; Amsterdam Public Health, Quality of Care, Amsterdam, the Netherlands; University of Groningen, University Medical Centre Groningen, Department of Primary Care and Long-Term Care, University Medical Centre Groningen, Groningen, the Netherlands.Carolina de Weerth – Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Centre.Arie Franx – Department of Obstetrics & Gynaecology, Erasmus University Medical Centre, Rotterdam, the Netherlands.Sam Harper – Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.Brenda M. Kazemier – Department of Obstetrics and Gynecology, Amsterdam UMC, University of Amsterdam, Meibergdreef 9, 1105, AZ, Amsterdam, The Netherlands.Peter Paul Klein – Department of Health Economics and Health Services Research, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, the Netherlands.Daniëlle Kretz – Department of Healthy Living, Public Health Service Amsterdam, the Netherlands.Jeremy Labrecque – Department of Epidemiology, Erasmus University Medical Centre, Rotterdam, the Netherlands.Ben Willem Mol – Department of Obstetrics & Gynaecology, Monash University, Melbourne, Australia.Jean Muris – Department of Obstetrics & Gynaecology, Erasmus University Medical Centre, Rotterdam, the Netherlands.Marianne Nieuwenhuijze – Research Centre for Midwifery Science Maastricht, Zuyd University / CAPHRI, Maastricht University, Maastricht, the Netherlands.Sylvia Obermann – Care4Neo, Neonatal patient and parent advocacy organization the Netherlands.Martijn Oudijk – Department of Obstetrics & Gynaecology, Amsterdam UMC, Amsterdam, the Netherlands.Lilian Peters- Amsterdam UMC Location Vrije Universiteit Amsterdam, Midwifery Science, Amsterdam, The Netherlands; Midwifery Academy Amsterdam Groningen, InHolland, Amsterdam, The Netherlands; Amsterdam Public Health, Quality of Care, Amsterdam, The Netherlands; Department of Primary and Long-term Care, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.Lotte Ramerman – Nivel, Netherlands Institute for Health Services Research, Utrecht, The Netherlands.Anita Ravelli – Department of Obstetrics & Gynaecology, Medical Informatics, Amsterdam UMC, Amsterdam, The Netherlands.Ageeth Schonewille-Rosman – Perined, Netherlands.Jeroen Struijs -Department of National Health and Healthcare, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands; Department of Public Health and Primary Care, Health Campus The Hague, Leiden University, The Hague, the Netherlands.Hanneke Torij – University of Applied Sciences, Rotterdam.Monique Van Beukering – Department of Obstetrics & Gynaecology, Amsterdam UMC, Amsterdam, the Netherlands.Thomas van den Akker – Department of Obstetrics & Gynaecology, Leiden University Medical Centre, Leiden, The Netherlands; Athena Institute, VU University, Amsterdam, The Netherlands.Marion van den Heuvel – Tranzo Scientific Centre for Care and Wellbeing, Tilburg University, Tilburg, The Netherlands.Jeroen van Dillen – Department of Obstetrics & Gynaecology, Radboud University Medical Centre, Nijmegen, the Netherlands.Frank van Lenthe – Department of Public Health, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands.Tom Van Ourti – Erasmus School of Health Policy & Management, Erasmus University Rotterdam, Rotterdam, the Netherlands; Erasmus School of Economics, Erasmus University Rotterdam, the Netherlands; Erasmus Centre for Health Economics Rotterdam, Erasmus University Rotterdam, The Netherlands; Tinbergen Institute, the Netherlands.Arnoud Verhoeff – Department of Healthy Living, Public Health Service Amsterdam, the Netherlands.Marijn Vermeulen – Department of Neonatal and Pediatric Intensive Care, Division of Neonatology, Erasmus Medical Centre-Sophia Children’s Hospital, Rotterdam, the Netherlands.Nettie Visser – UWV.Saskia Willers – Environmental Protection Agency, Schiedam, the Netherlands.Sam Schoenmakers – Department of Obstetrics and Gynaecology, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands.Zohra Zainularab – Department of Public Health, Erasmus University Medical Centre Rotterdam, Rotterdam, the Netherlands.Paper presentation information.This study was presented at the SMFM Global Meeting in Rome, 2024. This project was supported by ZonMW (Grant #05160482210001), Chiesi Pharmaceuticals, de Snoo-van ‘t Hoogerhuijs Foundation, and Strong Babies. The funders of the study were not involved in the study design, data collection, data analysis, interpretation, or the writing of the manuscript.

Funders	Funder number
Universiteit van Tilburg
Universiteit Maastricht
Netherlands.Hanneke Torij – University of Applied Sciences
Department of Neonatal and Paediatric Intensive Care
University Medical Centre Rotterdam
Tranzo Scientific Centre for Care and Wellbeing
Erasmus Centre for Health Economics Rotterdam
Netherlands.Marijn Vermeulen – Department of Neonatal and Pediatric Intensive Care
Public Health Service Amsterdam
Netherlands.Ben Willem Mol – Department of Obstetrics & Gynaecology
Leids Universitair Medisch Centrum
Department of National Health and Healthcare
Department of Genetics and Cell Biology, Faculty of Health, Medicine & Life Sciences, Maastricht University
Erasmus Universiteit Rotterdam
Netherlands.Loes Bertens – Department of Obstetrics and Gynaecology
Netherlands.Jeremy Labrecque – Department of Epidemiology
Netherlands.Ank de Jonge
Academie Verloskunde Amsterdam Groningen
Radboud Universiteit
Department of Primary Care
Division of Neonatology
Rijksuniversiteit Groningen
Erasmus Medical Centre-Sophia Children’s Hospital, Rotterdam
Universitair Medisch Centrum Groningen
Zuyd University
Radboud Universitair Medisch Centrum
Monash University
Athena Institute
Department of Public Health
Behavioural Science institute, Radboud University
Department of Obstetrics and Gynaecology
VU University
University Medical Centre Utrecht
Netherlands.Zohra Zainularab – Department of Public Health
McGill University
Netherlands.Marianne Nieuwenhuijze – Research Centre for Midwifery Science Maastricht
Erasmus School of Economics, Erasmus University Rotterdam
Tinbergen Institute
Nederlands Instituut voor Onderzoek van de Gezondheidszorg
Netherlands.Carolina de Weerth – Donders Institute for Brain, Cognition and Behavior, Radboud University
Department of Epidemiology, Biostatistics and Occupational Health, McGill University
Netherlands.Lex Burdorf – Department of Public Health
Children Hospital Birth Centre
Rijksinstituut voor Volksgezondheid en Milieu
Care and Public Health Research Institute, Universiteit Maastricht
Universiteit Leiden
UWV.Saskia Willers – Environmental Protection Agency
Chiesi Pharmaceuticals, de Snoo-van ‘t Hoogerhuijs Foundation
Erasmus University Medical Centre Rotterdam
Erasmus Universitair Medisch Centrum Rotterdam
Erasmus MC Sophia Kinderziekenhuis
ZonMw	05160482210001

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@article{9582a074762341f39f868b8e0a4e08c3,

title = "COVID-19 lockdown and association with placental function – a quasi-experimental analysis",

abstract = "Objective: To evaluate the effect of COVID-19 lockdown measures on the occurrence of hypertensive disorders of pregnancy and fetal growth restriction in a national pregnancy population.Study design: This is a national registry-based quasi-experimental study, including singleton births ≥24 + 0 weeks from nulliparous women between 2016–2020. We evaluated the effect of gestational age upon entering the first nationwide lockdown period (March 9th–June 1st 2020) on outcome. This effect can be assumed to be unconfounded (a so-called quasi-experimental analysis), because this period was unexpected and implemented rapidly, minimizing anticipatory changes at population level.Main outcome measures: Primary outcomes were hypertensive disorders of pregnancy (including pre-eclampsia) and small-for-gestational-age (birthweight <10th Hoftiezer percentile), as proxy for fetal growth restriction.Results: The analysis included 262,102 pregnancies. Compared to previous years, entering the lockdown in the first trimester was associated with an absolute +0.4\% risk of hypertensive disorders of pregnancy (95\%CI: +0.0\% – +0.8\%), +0.2\% risk of pre-eclampsia (95\%CI: +0.0\% – +0.4\%), but −0.5\% risk of small-for-gestational-age (95\%CI: −1.2 – –0.3). There was less evidence that other evaluated periods and trimesters were associated with the outcome.Conclusion: Being exposed to COVID 19 lockdown was associated with a slight increase in hypertensive disorders of pregnancy, including pre-eclampsia, but a counterintuitive trend towards lower risk for small-for-gestational-age. Because the effect was most clear in the first trimester, the nationwide lockdown therefore seems to have a complex effect on the in-utero environment through the placenta.",

author = "Gravesteijn, \{Benjamin Y.\} and Sam Schoenmakers and Nienke Boderie and \{van den Akker\}, Thomas and Auweele, \{Kim Vanden\} and Bertens, \{Loes C.M.\} and \{van Dillen\}, Jeroen and \{de Jonge\}, Ank and Kazemier, \{Brenda M.\} and Jeremy Labrecque and Mol, \{Ben Willem\} and Sylvia Oberman and Martijn Oudijk and \{Van Ourti\}, Tom and Peters, \{Lilian L.\} and Zainulareb Zohra and Been, \{Jasper V.\} and \{de Groot\}, \{Christianne J.\} and \{PREPARE Consortium\}",

note = "Publisher Copyright: {\textcopyright} 2026 The Author(s). Published by Elsevier B.V. on behalf of International Society for the Study of Hypertension in Pregnancy. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/",

year = "2026",

month = jun,

doi = "10.1016/j.preghy.2026.101452",

language = "English",

volume = "44",

pages = "1--9",

journal = "Pregnancy Hypertension",

issn = "2210-7789",

publisher = "Elsevier B.V.",

}

TY - JOUR

T1 - COVID-19 lockdown and association with placental function – a quasi-experimental analysis

AU - Gravesteijn, Benjamin Y.

AU - Schoenmakers, Sam

AU - Boderie, Nienke

AU - van den Akker, Thomas

AU - Auweele, Kim Vanden

AU - Bertens, Loes C.M.

AU - van Dillen, Jeroen

AU - de Jonge, Ank

AU - Kazemier, Brenda M.

AU - Labrecque, Jeremy

AU - Mol, Ben Willem

AU - Oberman, Sylvia

AU - Oudijk, Martijn

AU - Van Ourti, Tom

AU - Peters, Lilian L.

AU - Zohra, Zainulareb

AU - Been, Jasper V.

AU - de Groot, Christianne J.

AU - PREPARE Consortium

N1 - Publisher Copyright: © 2026 The Author(s). Published by Elsevier B.V. on behalf of International Society for the Study of Hypertension in Pregnancy. This is an open access article under the CC BY license. http://creativecommons.org/licenses/by/4.0/

PY - 2026/6

Y1 - 2026/6

N2 - Objective: To evaluate the effect of COVID-19 lockdown measures on the occurrence of hypertensive disorders of pregnancy and fetal growth restriction in a national pregnancy population.Study design: This is a national registry-based quasi-experimental study, including singleton births ≥24 + 0 weeks from nulliparous women between 2016–2020. We evaluated the effect of gestational age upon entering the first nationwide lockdown period (March 9th–June 1st 2020) on outcome. This effect can be assumed to be unconfounded (a so-called quasi-experimental analysis), because this period was unexpected and implemented rapidly, minimizing anticipatory changes at population level.Main outcome measures: Primary outcomes were hypertensive disorders of pregnancy (including pre-eclampsia) and small-for-gestational-age (birthweight <10th Hoftiezer percentile), as proxy for fetal growth restriction.Results: The analysis included 262,102 pregnancies. Compared to previous years, entering the lockdown in the first trimester was associated with an absolute +0.4% risk of hypertensive disorders of pregnancy (95%CI: +0.0% – +0.8%), +0.2% risk of pre-eclampsia (95%CI: +0.0% – +0.4%), but −0.5% risk of small-for-gestational-age (95%CI: −1.2 – –0.3). There was less evidence that other evaluated periods and trimesters were associated with the outcome.Conclusion: Being exposed to COVID 19 lockdown was associated with a slight increase in hypertensive disorders of pregnancy, including pre-eclampsia, but a counterintuitive trend towards lower risk for small-for-gestational-age. Because the effect was most clear in the first trimester, the nationwide lockdown therefore seems to have a complex effect on the in-utero environment through the placenta.

AB - Objective: To evaluate the effect of COVID-19 lockdown measures on the occurrence of hypertensive disorders of pregnancy and fetal growth restriction in a national pregnancy population.Study design: This is a national registry-based quasi-experimental study, including singleton births ≥24 + 0 weeks from nulliparous women between 2016–2020. We evaluated the effect of gestational age upon entering the first nationwide lockdown period (March 9th–June 1st 2020) on outcome. This effect can be assumed to be unconfounded (a so-called quasi-experimental analysis), because this period was unexpected and implemented rapidly, minimizing anticipatory changes at population level.Main outcome measures: Primary outcomes were hypertensive disorders of pregnancy (including pre-eclampsia) and small-for-gestational-age (birthweight <10th Hoftiezer percentile), as proxy for fetal growth restriction.Results: The analysis included 262,102 pregnancies. Compared to previous years, entering the lockdown in the first trimester was associated with an absolute +0.4% risk of hypertensive disorders of pregnancy (95%CI: +0.0% – +0.8%), +0.2% risk of pre-eclampsia (95%CI: +0.0% – +0.4%), but −0.5% risk of small-for-gestational-age (95%CI: −1.2 – –0.3). There was less evidence that other evaluated periods and trimesters were associated with the outcome.Conclusion: Being exposed to COVID 19 lockdown was associated with a slight increase in hypertensive disorders of pregnancy, including pre-eclampsia, but a counterintuitive trend towards lower risk for small-for-gestational-age. Because the effect was most clear in the first trimester, the nationwide lockdown therefore seems to have a complex effect on the in-utero environment through the placenta.

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COVID-19 lockdown and association with placental function – a quasi-experimental analysis

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